Trichomonas vaginalis is a parasitic protozoan, responsible for trichomoniasis, an infection of the urogenital tract which is one of the most common sexually transmitted diseases in the United States and in other parts of the world. Today, the treatment of trichomoniasis is based on the us of metronidazole and other nitroimidazole drugs, known to be carcinogenic in rodents, mutagenic in bacteria and teratogenic to the growing embryo and fetus. Pregnant women should not receive metronidazole, and in any case, it should not be given to patients over a long period of time. Moreover, it is known in the last years that metronidazole--resistant strains have emerged and this is a further reason to provide alternative means for the treatment of trichomoniasis.
In most cases, with proven trichomoniasis, high levels of antibodies to Trichomonas have been demonstrated. However, despite the fact that both humoral and cellular immune response can be demonstrated in these patients, protective immunity has not been effective and recurrent infections are very common. Attempts to stimulate the host's immune system against Trichomonas have been done by introducing a vaccine called Solco Trichovac, reported to be effective in the treatment of acute vaginal trichomoniasis and to be able to reduce the incidence of relapses. However, a vaccination plan is very costly and it requires repeated injections with only temporary efficiency.
In recent years, polyclonal antibodies (Alderete, J. F. 1983 Infect Immun. 39 1041-1047) as well as monoclonal antibodies (Torian B. E., Connelly, R. J., Stephens, R. S. and Stibbs, H. H. Infect. Immun. 1984, 43 270-275, Chang, T. H., Tsing, S. Y. and Tzeng, S. Hybridoma 1986, 5, 43-51), have been prepared against Trichomonas vaginalis in an attempt to study the antigenic nature of the parasite and to correlate it with its virulence.
In European Patent Application EP0141616, published on 24.10.85, monoclonal antibodies directed against Trichomonas vaginalis membrane protein antigens are disclosed and said to be useful in the purification and characterization of said membrane antigens, to facilitate studies on the vaccinogenic potential of said antigens and to he useful as diagnostic reagents for immunological assays for trichomoniasis infections.
In International Patent Application WO 86/02359 (PCT/GB 85/00470), published on 24.04.86, a monoclonal antibody specific for an antigen on species of Trichomonas is disclosed, mainly to be used in a labeled form in diagnosis. The monoclonal antibodies, including those directed against Trichomonas vaginalis, are also said to be useful in therapeutic compositions for the treatment of humans and/or animals, but no data on the lytic activity of the monoclonal antibodies is disclosed in order to support said affirmation.
In European Patent Application EP 0174874, published on 19.03.86, a monoclonal antibody specific for and cytolytic against Trichomonas vaginalis is disclosed and said to be useful in diagnosis or clinically for the prevention or treatment of trichomoniasis, when administered by oral route. It is very doubtful whether this monoclonal antibody administered by oral route will be useful at all for the treatment of trichomoniasis, since it will certainly be decomposed by proteolytic enzymes in the low pH vicinity of the stomach and will not reach the infection in the urogenital tract. Moreover, the monoclonal antibody is not sufficiently disclosed and Applicant's efforts to reproduce inherently cytolytic monoclonal antibody following the instructions given in said patent application have failed.
For all the above reasons there existed a real need for alternative means for treating trichomoniasis, a chronic disease which incidence is growing at a high rate in years. The present invention provides such alternative means in the form of monoclonal antibodies which by contact with the parasite would ensure the immediate lysis of Trichomonas without being negatively affected by the vaginal flora and/or the epithelial cells and which can be administered locally for treatment of trichomoniasis.